The immunomodulatory effects of bevacizumab on systemic immunity in patients with metastatic melanoma

Figures & data

Table 1. PBMC phenotypes*

Phenotype	ACB1	AC1	p	ACB2	AC2	CoVs	p
CD3^+	18 (−47–62)	5 (−39–50)	0.07	13 (−35–67)	0.4 (−33–31)	8.6	0.52
CD4^+	20 (−20–66)	15 (−43–63)	0.30	6 (−43–74)	7 (−40–36)	10.0	0.61
CD8^+	38 (−21–72)	−10 (−32–42)	0.03	23 (−38–87)	−1 (−35–54)	8.8	0.38
CD3^+/CD62L^+	23 (−25–115)	25 (−32–114)	0.91	20 (−48–90)	15 (−41–101)	26.6	0.93
TH1/TH2	9 (−13–41)	−3 (−25–43)	0.19	5.1 (−24–39)	−4 (−25–28)	14.7	0.28

* The median relative percent changes with interquartile ranges of peripheral blood mononuclear cell (PBMC) phenotypes are shown for patients who received one (1) or two (2) cycles of chemotherapy alone (AC) or combined with bevacizumab (ACB). We observed an increase in CD8⁺ cells in patients who received one cycle of chemotherapy plus bevacizumab as compared with those who received chemotherapy alone (p = 0.03). CoVs, coefficients of variation.

Figure 1. Changes in circulating CD8⁺ lymphocytes and interleukin-6 levels in melanoma patients receiving albumin-bound paclitaxel plus carboplatin alone or combined with bevacizumab. The median relative percent changes (RPCs) of CD8⁺ lymphocytes and circulating interleukin-6 (IL-6) levels are displayed for patients who received one (RPC1) or two (RPC2) cycles of chemotherapy alone (AC) or combined with bevacizumab (ACB). For CD8⁺ lymphocytes, the difference between patients receiving ACB and AB was significant after one (p = 0.03), but not after two (p = 0.38), cycles of therapy. For IL-6, the difference was significant after one (p = 0.01) as well as after two (p = 0.0018) cycles of therapy.

Table 2. Cytokines, chemokines and growth factors

Factor	ACB1	AC1	p	ACB2	AC2	CoV	p
EGF	−21 (−40 to 15)	−18 (−54 to 21)	0.55	−30 (−46–4)	−22 (−57–16)	20.1	0.80
Eotaxin (CCL11)	39 (−2 to 67)	20 (−5 to 47)	0.09	20 (−17–61)	16 (−13–42)	5.9	0.53
G-CSF	52 (−7 to 208)	81 (0 to 250)	0.56	4 (−43–171)	145 (−13–424)	24.2	0.56
GRO (CXCL1)	0 (−19 to 33)	−4 (−24 to 19)	0.42	−2 (−18–7)	−17 (−38–30)	20.7	0.29
IFNγ	−5 (−38 to 29)	0 (−39 to 29)	0.96	−23 (−60–7)	−23 (−49–12)	16.9	0.56
IL1b	0 (−19 to 21)	4 (−24 to 205)	0.19	0 (−86–19)	10 (−40–250)	6.3	0.05
IL2	0 (−38 to 2)	−2 (−27 to 4)	0.98	−6 (−50–0)	−9 (−41–8)	10.9	0.83
IL6	−16 (−63 to 38)	31 (−36 to 527)	0.01	−42 (−88–0)	28 (−37–480)	10.3	0.0018
IL8	1 (−46 to 94)	22 (−27 to 317)	0.48	113 (17–541)	13 (−44–284)	12.4	0.19
IL12p70	−7 (−33 to 5)	0 (−43 to 6)	0.84	−13(−55–0)	0 (−55–15)	21.3	0.77
IL17	−9 (−28 to 3)	0 (−42 to 13)	0.51	−26 (−54–0)	−23 (−59–14)	25.0	0.50
IP10 (CXCL10)	−19 (−41 to 24)	6 (−24 to 38)	0.11	−34 (−57–4)	3 (−41–37)	10.7	0.02
MCP1 (CCL2)	20 (-14 to 74)	20 (−14 to 100)	0.65	4 (-21–84)	17 (−22–50)	7.5	0.86
MCP3 (CCL7)	−12 (-39 to 4)	−1 (−47 to 85)	0.32	−18 (−54–9)	−4 (−42–122)	22.1	0.18
MDC (CCL22)	−12 (-22 to 4)	−4 (−20 to 10)	0.47	−10 (−26–15)	−12 (−25–13)	12.0	0.82
MIP1B (CCL4)	−6 (−44 to 38)	5 (−18 to 236)	0.22	−17 (−74–26)	0 (−50–160)	32.5	0.09
TGFα	−17 (−43 to 21)	−15 (−43 to 13)	1.00	−12 (−48–37)	−40 (−62–12)	25.6	0.07
TNFα	7 (−24 to 44)	20 (−32 to 95)	0.37	−22 (−59–11)	5 (−58–94)	26.4	0.03
VEGF	−29 (−51 to 0)	−21 (−42 to 7)	0.34	−49 (−79–−11)	−27 (−56–−7)	12.4	0.09

* The median relative percent changes with interquartile ranges of cytokine levels are shown for patients who received one (1) or two (2) cycles of chemotherapy alone (AC) or combined with bevacizumab (ACB). We observed a highly significant decrease in interleukin-6 IL-6 levels (p = 0.0018) after two cycles of therapy. CoVs, coefficients of variation; EGF, epithelial growth factor; G-CSF, granulocyte colony-stimulating factor; IFNγ, interferon γ; IP10, IFNγ-inducible protein 10; MCP, monocyte chemoattractant protein; MDC, macrophage-derived chemokine; MIP1B, macrophage inflammatory protein 1B; TNFα, tumor necrosis factor α; TGFβ, transforming growth factor β; VEGF, vascular endothelial growth factor.